The role of catecholamines on intercellular coupling, myocardial cell synchronization and self ventricular defibrillation

Tedisamil is antiarrhythmic class III drug with antifibrillating/defibrillating potency linked to enhancement of intermyocyte gap junctional electrical coupling most likely via its sympathomimetic cAMP-related mechanisms. This study was designed to examine the effect of tedisamil on cAMP level in guinea pig hearts in vivo and in vitro in Langendorff preparation. The drug was administered either as a bolus into vena jugularis in dosage 1.0 and 1.5 mg/kg or into the perfusion solution at a concentration of 1.5 x 10(-6) mol/l. In additional experiments, this period was followed by brief 10 min global ischemia, induced by clamping of the aorta or perfusion. After 10 min from the onset of tedisamil administration as well as after 10 min of ischemia the ventricular tissue was immediately frozen for cAMP immunoassay. Tedisamil caused in normal heart small but significant dose-dependent increase of myocardial cAMP (pmol/mg) level in vivo 1.8 and 2.5 vs. 1.4 as well as in vitro 1.1 vs. 0.8 (p < 0.05) conditions. Ischemia itself induced accumulation of cAMP in both, in vivo and in vitro experiments, 2.6 vs. 1.4 and 1.3 vs. 0.8, respectively. The preischemic elevation of cAMP by tedisamil was not potentiated by following ischemia, on the contrary, decline of the cyclic nucleotide was detected comparing to ischemia itself. In conclusion, tedisamil increased cAMP level in normal heart and prevented additional ischemia-related elevation of this nucleotide. The results indicate modulation of myocardial cAMP level by tedisamil, which may account for its protective effect on gap junctional electrical coupling.

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Tribulová

Ravingerová

Okruhlicová

et al. 2000

Molecular and Cellular Biochemistry

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Differential effects of defibrillation on systemic and cardiac sympathetic activity

Bode

Wiegand

Raasch

et al. 1998

Heart

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Objective-To assess the eVect of defibrillation shocks on cardiac and circulating catecholamines. Design-Prospective examination of myocardial catecholamine balance during dc shock by simultaneous determination of arterial and coronary sinus plasma concentrations. Internal countershocks (10-34 J) were applied in 30 patients after initiation of ventricular fibrillation for a routine implantable cardioverter defibrillator test. Another 10 patients were externally cardioverted (50-360 J) for atrial fibrillation. Main outcome measures-Transcardiac noradrenaline, adrenaline, and lactate gradients immediately after the shock. Results-After internal shock, arterial noradrenaline increased from a mean (SD) of 263 (128) pg/ml at baseline to 370 (148) pg/ml (p = 0.001), while coronary sinus noradrenaline fell from 448 (292) to 363 (216) pg/ml (p = 0.01), reflecting a shift from cardiac net release to net uptake. After external shock delivery, there was a similar increase in arterial noradrenaline, from 260 (112) to 459 (200) pg/ml (p = 0.03), while coronary sinus noradrenaline remained unchanged. Systemic adrenaline increased 11-fold after external shock (p = 0.01), outlasting the threefold rise following internal shock (p = 0.001). In both groups, a negative transmyocardial adrenaline gradient at baseline decreased further, indicating enhanced myocardial uptake. Cardiac lactate production occurred after ventricular fibrillation and internal shock, but not after external cardioversion, so the neurohumoral changes resulted from the defibrillation process and not from alterations in oxidative metabolism. Conclusions-A dc shock induces marked systemic sympathoadrenal and sympathoneuronal activation, but attenuates cardiac sympathetic activity. This might promote the transient myocardial depression observed after electrical discharge to the heart. (Heart 1998;79:560-567)

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Myocardial electrotonic response to submaximal exercise in dogs with healed myocardial infarctions: evidence for Î²-adrenoceptor mediated enhanced coupling during exercise testing

Río

Clymer

2015

Front. Physiol.

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Introduction: Autonomic neural activation during cardiac stress testing is an established risk-stratification tool in post-myocardial infarction (MI) patients. However, autonomic activation can also modulate myocardial electrotonic coupling, a known factor to contribute to the genesis of arrhythmias. The present study tested the hypothesis that exercise-induced autonomic neural activation modulates electrotonic coupling (as measured by myocardial electrical impedance, MEI) in post-MI animals shown to be susceptible or resistant to ventricular fibrillation (VF).Methods: Dogs (n = 25) with healed MI instrumented for MEI measurements were trained to run on a treadmill and classified based on their susceptibility to VF (12 susceptible, 9 resistant). MEI and ECGs were recorded during 6-stage exercise tests (18 min/test; peak: 6.4 km/h @ 16%) performed under control conditions, and following complete β-adrenoceptor (β-AR) blockade (propranolol); MEI was also measured at rest during escalating β-AR stimulation (isoproterenol) or overdrive-pacing.Results: Exercise progressively increased heart rate (HR) and reduced heart rate variability (HRV). In parallel, MEI decreased gradually (enhanced electrotonic coupling) with exercise; at peak exercise, MEI was reduced by 5.3 ± 0.4% (or -23 ± 1.8Ω, P < 0.001). Notably, exercise-mediated electrotonic changes were linearly predicted by the degree of autonomic activation, as indicated by changes in either HR or in HRV (P < 0.001). Indeed, β-AR blockade attenuated the MEI response to exercise while direct β-AR stimulation (at rest) triggered MEI decreases comparable to those observed during exercise; ventricular pacing had no significant effects on MEI. Finally, animals prone to VF had a significantly larger MEI response to exercise.Conclusions: These data suggest that β-AR activation during exercise can acutely enhance electrotonic coupling in the myocardium, particularly in dogs susceptible to ischemia-induced VF.

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The role of catecholamines on intercellular coupling, myocardial cell synchronization and self ventricular defibrillation

Cited by 3 publications

References 46 publications

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Differential effects of defibrillation on systemic and cardiac sympathetic activity

Myocardial electrotonic response to submaximal exercise in dogs with healed myocardial infarctions: evidence for Î²-adrenoceptor mediated enhanced coupling during exercise testing

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